Wang, Amy

Adolescents and young adults (AYA; ages 15–39) with acute leukemia have significant unmet supportive care needs. This pilot study integrated same-day palliative care (PC) into an AYA leukemia clinic, measuring symptom burden (SB) with validated symptom assessment tools at baseline, 3, and 6 months. Among 31 patients, moderate-severe symptoms included tiredness, anxiety, and poor appetite. AYAs experienced high SB and psychological distress, regardless of care phase or sociodemographics. With PC integration, tiredness and depression improved significantly; no symptoms worsened. Half of the PC visits led to management changes. Early integration of symptom-focused PC was feasible, value-adding, and well-received by patients.

BackgroundThe availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B‐cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity.MethodsIn this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared.ResultsAmong 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety‐two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09).ConclusionsAlthough the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.

Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate composed of anti-CD22 antibody conjugated to the cytotoxic agent calicheamicin, which is approved for relapsed/ refractory (RR) B-cell acute lymphocytic leukemia (ALL), based on efficacy demonstrated in a randomized control trial. We sought to investigate the safety and efficacy of InO in the "real world" setting. Methods: We conducted a retrospective multicenter study in collaboration with 11 U.S. academic institutions, and evaluated the outcome of patients (pts) with RR B-cell ALL, who received InO outside of clinical trials. These pts were evaluated for response to InO, duration of response, overall survival (OS) and toxicity. Demographic and disease characteristics were summarized using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method and compared via log-rank test. Duration of response was estimated among pts who achieve complete remission (CR)/CR with incomplete count recovery (CRi). Results: From June 2016 to May 2019, 84 pts with RR-B cell ALL were identified. Baseline characteristics are summarized in Table 1. The median age of pts at InO initiation was 50 years (yrs) (range, 20-87). Twenty-two (27.5%) pts had t(9;22) (Ph+ve) and 6 (7.5%) pts had t(4;11) (MLL gene) chromosomal abnormalities. Nine (11%) and 20 (25%) pts had CNS disease at diagnosis and at relapse, respectively. Median number of therapies prior to InO was 2 (range, 0-7), 40 (48%) pts had ≥ 3 therapies and 23 (27%) pts had allogeneic stem cell transplantation (allo-HCT) prior to InO. Forty (48%) pts received blinatumomab prior to InO. Fourteen (17%) pts received InO in combination with chemotherapy and/ or tyrosine kinase inhibitor (TKI). Overall response rate (CR/CRi) was 63%; 44% had CR with minimal residual disease (MRD) negativity by flow cytometry. Response rate in Ph+ve B-cell ALL was 73%. Twenty-three (27%) pts were successfully bridged to allo-HCT. Median response duration with InO was 11.5 months (mo); 32.5% had sustained response at 2 yrs (Fig. 1a). Median response duration post InO, censored at allo-HCT was not reached (NR) (51% in remission at 2 yrs) (Fig. 1b). Median OS after InO was 11.6 mo and 32% were alive at 2 yrs (Fig. 1c). Median OS post InO, censored at of allo-HCT was 13.6 mo (Fig. 1d). Median OS after InO in Ph+ve pts was NR (71% alive at 1 yr). Forty-nine percent, 27%, 6% and 5% of pts discontinued InO due to progression, allo-HCT, adverse events and maintenance therapy, respectively. Nineteen (30%) pts had dose interruptions. In terms of toxicities, 14 (17%) and 7 (8%) pts had grade (G)1-2 and G3 transaminases secondary to InO, respectively. One pt each had G2 and G3 pancreatitis, respectively. One (1%) and 2 (2%) pts had G2 and G4 veno-occlusive disease secondary to InO, respectively. Two of these pts were treated with defibrotide. Two (2%) pts died due to InO toxicity. A complete description of adverse events are summarized in Table 1. Conclusion: Our real-world data obtained by multicenter collaboration suggest that InO was well tolerated and had significant efficacy in this heavily treated patient population of RR B-cell ALL. Disclosures Liedtke: Celator: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Agios: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding. Aldoss:Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria; AUTO1: Consultancy; Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses. Curran:Incyte: Research Funding; Merck: Research Funding; Gilead: Research Funding. Podoltsev:Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Samus Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; Kartos Therapeutics: Research Funding; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Yang:AstraZeneca: Research Funding; Agios: Consultancy. Mattison:Pfizer: Membership on an entity's Board of Directors or advisory committees. Advani:Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Research Funding; Kite Pharmaceuticals: Consultancy; Abbvie: Research Funding. Atallah:Takeda: Consultancy, Research Funding; Jazz: Consultancy; Helsinn: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy.

242 Background: We evaluated plasma cell free based genomic aberrations for prognosticating survival of newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patients (pts). Methods: Plasma was collected from mHSPC pts enrolled between 2009-2014. Platelet poor plasma (PPP) fractions were processed uniformly and cell free DNA (cfDNA) extracted using Qiagen kits. Pts were followed after initiating hormonal therapy until death. Next Gen Sequencing (NGS) of cfDNA was performed using Illumina HiSeq X for a preselected panel of 128 genes (PredicineDDR-77 cancer driver genes; 29 genes in BRCA-FA homologous recombination deficiency (HRD) pathway; 22 DNA damage repair pathway genes). Statistical analyses of plasma genome based aberrations with overall survival (OS) were performed in R 3.5.1. Cox proportional-hazard models were used for survival analysis. Results: An average of 2.5 ml PPP from 99 pts yielded a median of 10.5 ng (range: 2.8-702) cfDNA per sample. 15/99 pt samples with a yield < 5 ng were excluded from sequencing; 9/99 samples failed NGS. Median follow-up time was 80.2 months (mths) (Range: 74.7, 87]); median OS was 69.1 mths (range: 54,NR). 29 pts with full NGS data had high volume metastatic disease. cfDNA yield correlated with metastatic volume (P = 0.01). Univariate analysis revealed both variables prognostic for OS (Metastatic volume: log-rank P=0.01, HR=2.1, 95% CI: 1.1-3.8; cfDNA yield: P =0.04, HR = 1.3, 95% CI: 1.03-1.7). Multivariate regression showed prognostic value of cfDNA yield remained independent of metastatic volume (P = 0.03, HR = 1.34, 95% CI: 1.02-1.76). 54/67 samples with NGS data had at least one mutation/copy number variation detected. Top mutated genes included TP53 (N=18), ATM (N=9), CHEK2 (N=7), FANCM (N=6), RB1 (N=6), BRCA2 (N=5), PIK3CA (N=4) and 37/67 pts harbored 1≥ variant in HDR pathways. These pts had a shorter survival (median: 58.6 mths) (P=0.04, HR= 2.28, 95% CI: 1.01-5.18) and pts with ATM mutations did significantly worse (median survival: 47.4 mths) (HR=4.03, P=0.0005, 95% CI: 1.73-9.37). Conclusions: Plasma cfDNA yield is prognostic for survival in newly diagnosed mHSPC state and presence of HRD pathway genomic aberrations in plasma cfDNA are associated with poor survival.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. Objective: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. Data Sources: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). Study Selection: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. Data Extraction: Two authors performed the data extraction independently. Data Synthesis: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, −2.3 mg/dL; 95% confidence interval, −4.5 to −0.1, I2 = 72%, P = .04) and fasting blood insulin (weighted mean difference, −2.1 μU/mL, 95% confidence interval, −3.3 to −1.0, I2 = 0%, P &lt; .001). Changes in body mass index were associated with changes in fasting blood glucose (P &lt; .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. Conclusions: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.